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Age-related gene expression in tissues of the long-lived red sea urchin

ABSTRACT: The red sea urchin, Mesocentrotus franciscanus, is one the earth’s longest-lived animals, reported to live more than 100 years with indeterminate growth, life-long reproduction and no increase in mortality rate with age. To explore the idea that transcriptional stability is a key determinant of longevity and negligible senescence, age-related gene expression was examined in three tissues of the red sea urchin (Aristotle’s lantern muscle, esophagus and radial nerve cord). Genome-wide transcriptional profiling using RNA-Seq revealed remarkable stability in muscle and esophagus with very few age-related changes in gene expression. In contrast, expression of more than 900 genes was significantly altered with age in radial nerve cord including genes involved in nerve function, signaling, metabolism, cytoskeleton, transcriptional regulation and chromatin modification. Notably, there was an upregulation in expression of genes involved in synaptogenesis and axonogenesis suggesting enhanced nervous system activity with age. Among the signaling pathways affected by age, there was a downregulation in expression of key components of the mTOR signaling pathway and an upregulation of negative regulators of this pathway. This was accompanied by a reduction in expression of genes involved in protein synthesis and mitochondrial function and an increase in expression of genes that promote autophagy. Downregulation of the mTOR pathway together with the other observed changes reveals a unique age-related gene expression profile in the red sea urchin nervous system that may contribute to mitigation of the detrimental effects of aging in this long-lived animal.

ORGANISM(S): Mesocentrotus franciscanus

PROVIDER: GSE136352 | GEO | 2020/06/08

REPOSITORIES: GEO

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Project description:Purpose: The Tbrain transcription factor has demonstrated an evolved preference for low-affinity, secondary site binding motifs between the sea star and sea urchin orthologs. We sought to identify targets of sea urchin and sea star orthologs of Tbr. Because less is known about the function of Tbr during sea star development, we used RNA-seq in conjuction with ChIP-seq studies (GEO:xxxx) to determine the targets of sea star Tbr in early development. Methods: Sea star (Patiria miniata) embryos were injected with translation-blocking morpholino antisense oligonucleotides to knock-down PmTbr expression, as described previously. Control morpholinos were injected into sibling embryos. Embryos were allowed to develop until hatching (30-36 hpf) at which point injected embryos were collected and RNA was extracted. RNA-seq libraries were prepared, sequenced, and analyzed using standard protocols. Results: There are 2,562 genes that are significantly differentially expressed relative to control morpholino inected embryos (FDR < 0.05). There are roughly equivalent numbers of genes down-regulated (1,041) and up-regulated (1,521) by Pm-tbr knockdown, suggesting that PmTbr may act as both a transcriptional activator and repressor. 1,165 differentially expressed genes are located within 75 kb of a PmTbr binding site determined using ChIP-seq, and this set is used as a basis for comparison between sea star and sea urchin binding sites. Conclusions: 1,165 targets of the PmTbr transcription factor were identified based on differential expression following knockdown and the presence of transcription factor binding sites proximal to differentially expressed genes. There are an equal number of up- and down-regulated targets, suggesting Tbr may function as a transcriptional activator and repressor, depending on context and target gene. There was no clear association of motif utilization with either the direction of differential expression or ontological category of the target gene. There are only a small fraction of target genes (approximately 10%) that are in common between the sea star and sea urchin sets.

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Age-related gene expression in tissues of the long-lived red sea urchin

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